Evaluation of subchronic (13 weeks) and reproductive toxicity potential of intravaginal gel-microemulsion formulation of a dual-function phenyl phosphate derivative of bromo-methoxy zidovudine (compound WHI-05) in B6C3F1 mice

Contraception

Volumn 61, Issue 1, 2000, Pages 69-76

  D'Cruz, Osmond J ^a   Waurzyniak, Barbara ^a   Yiv, Seang H ^a   Uckun, Fatih M ^b  

^a PARKER HUGHES INSTITUTE   (United States)

^b Parker Hughes Clinics   (United States)

Author keywords

13 week intravaginal; HIV AIDS; Microbicide; Zidovudine

Indexed keywords

5 BROMO 5,6 DIHYDRO 6 METHOXY 3' AZIDOTHYMIDINE 5' (4 METHOXYPHENYL)METHOXYALANINYL PHOSPHATE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; SPERMICIDAL AGENT; UNCLASSIFIED DRUG; ZIDOVUDINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CHRONIC TOXICITY; CONTROLLED STUDY; FEMALE; GEL; HISTOPATHOLOGY; MICROEMULSION; MOUSE; NONHUMAN; REPRODUCTIVE TOXICITY;

ACQUIRED IMMUNODEFICIENCY SYNDROME; ADMINISTRATION, INTRAVAGINAL; ANIMALS; ANTI-HIV AGENTS; BLOOD CELL COUNT; BLOOD CHEMICAL ANALYSIS; EMULSIONS; FEMALE; FERTILITY; GELS; MALE; MICE; ORGAN SIZE; THYMIDINE MONOPHOSPHATE; ZIDOVUDINE;

EID: 0034022390     PISSN: 00107824     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0010-7824(99)00118-3     Document Type: Article

References (17)

1. Quinn T.C. Global burden of the HIV pandemic. Lancet. 348:1996;99-106.
2. Ward J.W., Duchin J.S. The epidemiology of HIV and AIDS in the United States. AIDS Clin Rev. 98:1997;1-45.
3. CDCP Update. US HIV and AIDS cases reported through December 1996. HIV/AIDS Surveillance Report 1997;8:1-33.
4. Sallio S.D., Kurtzman J.T., Radner A.B. HIV infection in women an escalating health concern . Am Fam Physician. 54:1996;1541-1548.
5. Davis S.F., Rosen D.H., Steinberg S., Wortley P.M., Karon J.M., Gwinn M. Trends in HIV prevalence among childbearing women in the United States, 1989-1994. J Acquir Immune Defic Syndr Hum Retrovirol. 19:1998;158-164.
6. Cookson C. WHO to concentrate HIV strategy on vaginal microbicides. Br Med J. 307:1993;1375-1376.
7. Lange J.M.A., Karam M., Piot P. Boost for vaginal microbicides against HIV. Lancet. 341:1993;1356-1359.
8. D'Cruz O.J., Venkatachalam T.K., Zhu Z., Shih M., Uckun F.M. Bromo-methoxy and aryl phosphate derivatives of azidothymidine are dual function spermicides with potent anti-HIV activity. Biol Reprod. 59:1998;503-515.
9. D'Cruz O.J., Shih M.-J., Yiv S.H., Chen C.-L., Uckun F.M. Synthesis, characterization and preclinical formulation of a novel phenyl phosphate derivative of bromo-methoxy zidovudine (compound WHI-07) with potent anti-HIV and spermicidal activities. Mol Hum Reprod. 5:1999;421-432.
10. D'Cruz O.J., Zhu Z., Yiv S.H., Chen C.-L., Waurzyniak B., Uckun F.M. WHI-05, a novel bromo-methoxy substituted phenyl phosphate derivative of zidovudine is a dual-action spermicide with potent anti-HIV activity. Contraception. 59:1999;319-331.
11. Richmann D.D., Fischl M.A., Grieco M.H., et al. The toxicity of AZT in the treatment of patients with AIDS and AIDS-related complex. N Engl J Med. 317:1987;192-197.
12. Pluda J.M., Mitsuya H., Yarchoan R. Hematologic effects of AIDS therapies. Hematol Oncol Clin North Am. 5:1991;229-248.
13. Thompson M.B., Dunnick J.K., Sutphin M.E., Giles H.D., Irwin R.D., Prejean J.D. Hematologic toxicity of AZT and ddC administered as single agents and in combination to rats and mice. Fundament Appl Toxicol. 17:1991;159-176.
14. Eccleston GM. Microemulsion. In: Swarbrick J, Boylan JC, eds. Encyclopedia of Pharmaceutical Technology. New York: Marcel Dekker, 1992:375-421.
15. Ritschel W.A. Microemulsions for improved peptide absorption from the gastrointestinal tract. Meth Find Exp Clin Pharmacol. 13:1993;205-220.
16. Guide for the Care and Use of Laboratory Animals. National Research Council. National Academy Press, 1996.
17. McGuigan C., Kinchington D., Nicholls R., Nickson C., O'Connor T.J. Kinase bypass a new strategy for anti-HIV drug design . Bioorg Med Chem Lett. 3:1993;1207-1210.